Heme binding compounds and use thereof

Abstract

Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of α 1 adrenergic agonists are physiologically active compounds including N.sup.δ -substituted ornithine or N.sup.ε -substituted lysine moieties or monoalkyl carbon-substituted N.sup.δ -substituted ornithine or N.sup.ε -substituted lysine moieties, having the formula ##STR1## wherein R is (CH 2 ) y CH 3 or H, R' is CH 2 or C(H)(CH 2 ) y CH 3 , and R" is CH 2 or C(H)(CH 2 ) y CH 3 , with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is a heme binding moiety and/or a sulfur-containing binding moiety and Q' is --NH 2 when there is a double bond between the omega carbon and Q and Q' is ═NH when there is a single bond between the omega carbon and Q, and physiologically acceptable acid addition salts thereof.

What is claimed is: 
     
       1. Physiologically active arginine or citrulline antagonist compounds including N.sup.δ -substituted ornithine or N.sup.ε -substituted lysine moieties or monoalkyl carbon-substituted N.sup.δ -substituted ornithine or N.sup.ε -substituted lysine moieties, having the formula ##STR9## wherein R is (CH 2 ) y  CH 3  or H, R' is CH 2  or C(H) (CH 2 ) y  CH 3 , and R" is CH 2  or C(H) (CH 2 ) y  CH 3 , with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is a nitrogen containing heme binding moiety and Q' is --NH 2  when there is a double bond between the omega carbon and Q and Q' is ═NH when there is a single bond between the omega carbon and Q, and physiologically acceptable acid addition salts thereof. 
     
     
       2. The physiologically active compounds of claim 1 wherein the heme binding moiety constituting Q is a nitrogen-containing heme binding moiety.